Personalized prosthesis and methods of use

ABSTRACT

A personalized prosthesis for implantation at a treatment site of a patient includes a self-expanding mesh or membrane having collapsed and expanded configurations. The collapsed configuration is adapted to be delivered to the treatment site, and the expanded configuration engages the personalized prosthesis with the treatment site. The mesh or membrane is personalized to match the treatment site in the expanded configuration, and has an outer surface that substantially matches the treatment site shape and size. The self-expanding mesh or membrane forms a central lumen configured to allow blood or other body fluids to flow therethrough. Methods of manufacturing and delivery of the personalized prosthesis are also disclosed.

CROSS-REFERENCE

The present application is a non-provisional of, and claims the benefitof U.S. Provisional Patent Application No. 61/554,099 (Attorney DocketNo. 22520-703.101) filed Nov. 1, 2011; the entire contents of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present application generally relates to medical prostheses, methodsfor fabricating the prostheses, and methods for treating diseased ordamaged tissue. More specifically, the present application relates totreatment of blood vessels or other body lumens and body cavities,including aneurysms such as in the aorta or in the brain.

An aneurysm is the localized dilation of a blood vessel which presents aserious medical condition. Such distention is the result of localizedweakening of the vessel often caused by atherosclerosis, infection, orcongenital defects. Most commonly aneurysms occur in arteries at thebase of the brain or in the aorta. Cases of significant distention riskthe possibility of vessel rupture and the resulting internal hemorrhageis a life threatening medical emergency that requires immediate surgicalintervention. Aneurysms that are large enough to present an unacceptablelevel of risk of rupture are treated with preemptive surgery.

The most reliable surgical remedy for aneurysms is excision of theaneurysm and repair of the afflicted blood vessel with a graft. However,this procedure requires highly invasive surgery and often requiresclamping of a major vessel such as the aorta, which can place a largestrain on the patient's heart. Patients requiring aneurysm treatmentoften have co-morbid risk factors such as diabetes, heart disease, andhypertension, and thus such patients can be poor candidates for such astressful operation. Accordingly, newer endovascular grafting methodsfor minimally invasive intervention of aneurysms are favored overtraditional grafts for some patients. These endovascular installedgrafts or “endoluminal grafts” are installed by accessing the aneurysmthrough the iliac arteries and have stent-like scaffolding supports atits terminal ends. Endoluminal grafts, however, in some situations aremore prone to post-operative complications than traditionally installedgrafts. Within two years of installation, a significant number of aorticendoluminal grafts exhibit leakage at the proximal interface to theaorta, necessitating further endovascular surgical intervention.Additionally, a small portion of endoluminal grafts drift inside therepaired blood vessel and expose the aneurysm. Repair of a drifted graftrequires open surgery in a patient who is likely a poor candidate forsuch a procedure.

Endoluminal grafting must overcome geometrical problems stemming frommorphological variations in aneurysm presentation and location. Whilemost aneurysms are “fusiform,” exhibiting distention along the entirecircumference of the afflicted blood vessel, varied geometries exist.Some aneurysms display ballooning of the vessel on one side at a narrowneck (also referred to as saccular), or may have otherwise treacherousgeometries. Other aneurysms may be located in close proximity tosensitive structures such as renal arteries. Endoluminal grafts incertain situations may encounter higher incidence of failure withnon-fusiform geometries and may be unsuitable for implantation where theimplants and their delivery techniques prove too incompatible orcumbersome for aneurysm geometry or location.

Given these concerns, there is strong unmet need for improvedendoluminal grafts and delivery methods. Such an improved designpreferably facilitates more reliable repair of aneurysms over a widerspace of geometries and the ability to be delivered with such finesse asto shorten procedure time and expand the number of aneurysms that aretreatable endovascularly. It would also be desirable if such improvedendoluminal grafts also fit the patient's anatomy more accurately andtherefore help prevent endoleaks and more securely anchor the endograftin the aneurysm and prevent drifting. At least some of these objectiveswill be met by the devices described herein.

2. Description of Background Art

Patents and Publications related to personalizable implants include butare not limited to U.S. Pat. Nos. 7,799,047; 7,769,603; 7,483,558;7,201,762; 7,029,487; 6,500,190; 6,165,193; 4,436,684; and U.S. PatentPublication Nos. 2011/0016690; 2008/0228216; 2008/0039923; and2006/0058638.

SUMMARY OF THE INVENTION

The present application generally relates to medical prostheses, methodsfor manufacturing the prostheses, and methods for treating diseased ordamaged tissue. More specifically, the present application relates totreatment of blood vessels or other body lumens and body cavities,including aneurysms such as in the aorta, other arteries, or in thebrain arteries. The techniques disclosed herein generally result in apersonalized prosthesis that is designed and manufactured to match theanatomy of the patient's diseased or damaged tissue. The personalizedprostheses may be commercially distributed once appropriate regulatoryapprovals have been obtained (e.g. Food and Drug Administration), andare not necessarily the same as “custom devices” defined in 21 CFR§812.3(b), which applies to non-commercial distribution of medicaldevices under certain circumstances, such as compassionate use.

The prostheses disclosed herein, such as mesh alone, covered mesh, ormembrane alone may be implanted into a treatment site such as ananeurysm to stabilize the aneurysm and to help prevent it from growinglarger. This applies to incipient aneurysms (e.g. untreated early stageaneurysms usually less than 50 mm in diameter) or larger, later stageaneurysms may also be treated using the prostheses described herein.

In a first aspect of the present invention, a method for manufacturing apersonalized implantable prosthesis in a manufacturing facilitycomprises providing one or more images of a treatment site in a patientand creating a digital data set characterizing shape and volume of thetreatment site based on the one or more images. The method alsocomprises transforming the digital data set into machining orfabrication instructions, and forming a mandrel using the machining orfabrication instructions. The mandrel has a shape that substantiallymatches the treatment site shape. The method further comprises applyinga mesh to the mandrel, heat treating the mesh while the mesh is disposedover the mandrel so that the mesh is biased to return to a shapematching the shape of the treatment site, and optionally forming amembrane over the mesh thereby forming the personalized implantableprosthesis. The personalized implantable prosthesis has a contractedconfiguration and an expanded configuration. The personalizedimplantable prosthesis is adapted to be delivered to the treatment sitein the contracted configuration, and the personalized implantableprosthesis is biased to return to the expanded configuration. Theexpanded configuration has a shape substantially matching or conformingto the treatment site shape and volume. Once the expanded personalizedprosthesis is deployed at the treatment site, it may be anchored intothe tissue and may provide support to the tissue. In the case of ananeurysm, the prosthesis prevents further expansion of the walls of theaneurysm.

Providing the one or more images may comprise providing one or morecomputerized tomography (CT) images, one or more magnetic resonanceimages (MRI), one or more x-ray images, one or more ultrasound images,or one or more an angiography images of the treatment site. Transformingthe digital data set into machining instructions may comprisetransferring the digital data set into a computer automateddesign/computer aided manufacturing (CAD/CAM) system. Forming themandrel may comprise machining a piece of metal which may be undersizedrelative to the treatment site. The undersized mandrel may accommodatefor thickness of the mesh and/or the membrane disposed thereover.

Applying the mesh to the mandrel may comprise slidably disposing a meshover the mandrel, or wrapping a filament around the mandrel. The meshmay also be a preformed flat mesh which is wrapped around the mandrelwith the ends of the mesh affixed to one another. Heat treating the meshmay comprise heat treating a nitinol mesh. The mandrel may be removedfrom the mesh so that the mesh may be recovered. At least one sideaperture may be formed in the prosthesis, and the at least one sideaperture may be configured to be aligned with a side branch vessel inthe treatment site. Forming the membrane may comprise attaching apolymer cover to the mesh, or dip coating a polymer cover over the meshthereby creating a personalized implantable prosthesis. The membrane maybe biodegradable. The implantable prosthesis preferably is removed fromthe mandrel thereby forming a central lumen which extends through theprosthesis. The mandrel may be removed from the mesh and then the meshmay be recovered for further processing. In other embodiments, a covermay be applied directly over the mandrel to form the prosthesis with orwithout a mesh layer. The cover may be a polymer (e.g. expandedpolytetrafluoroethylene), a fabric (e.g. Dacron), or other materialsknown in the art.

The method may further comprise the steps of mounting the implantableprosthesis on a delivery catheter, cleaning the implantable prosthesisand delivery catheter, packaging the implantable prosthesis, andterminally sterilizing the implantable prosthesis. The prosthesismounted on the delivery system may then be shipped from themanufacturing facility to a hospital or other location. The method mayalso comprise mounting the personalized implantable prosthesis on adelivery catheter, placing the personalized implantable prosthesis andthe delivery catheter in packaging, sterilizing the prosthesis anddelivery catheter in the packaging, and requesting verification that thepersonalized implantable prosthesis is appropriate for implantation atthe treatment site before shipping the personalized implantableprosthesis from the manufacturing facility. Verification may also occurprior to opening the sterile packaging holding the personalizedimplantable prosthesis. Verification may be performed by a physician,and may be performed over the Internet. The method may further compriseforming at least one side aperture in the personalized implantableprosthesis which can be aligned with a side branch vessel in thetreatment site. The treatment site may be an aneurysm.

In another aspect of the present invention, a personalized prosthesisfor implantation at a treatment site comprises a self-expanding meshhaving a collapsed configuration and an expanded configuration. Thecollapsed configuration is adapted to be delivered to the treatmentsite, and the expanded configuration is adapted to expand thepersonalized prosthesis into engagement with the treatment site. Themesh in the expanded configuration is personalized to conform to orotherwise match the treatment site. The mesh has an outer surface thatsubstantially matches the treatment site shape and size in the expandedconfiguration, and the self-expanding mesh forms a central lumen that isconfigured to allow blood or other body fluids to pass therethrough.

The self-expanding mesh may comprise a nitinol mesh, or it may compriseone or more filaments in a helical pattern. The mesh may also comprisebarbs or hooks adapted to engage tissue at the treatment site and anchorthe prosthesis. The mesh may also comprise a plurality of overlappingfilaments forming twisted or overlapping regions. The overlappingregions form raised surfaces that may be adapted to engage tissue at thetreatment site and anchor the prosthesis. The one or more filaments maybe woven together to form overlapping regions with the filamentsoverlapping one another at least once, twice, three times, or more. Inother embodiments, some of the overlapping regions may have a firstnumber of overlaps of the filaments while in other overlapping regionsthere may be a second number of overlaps different than the firstnumber.

The prosthesis may also comprise a biodegradable or non-biodegradablemembrane disposed over the mesh. The membrane may be elastic and mayconform to the self-expanding mesh. The membrane may have an outersurface that substantially matches the treatment site shape in theexpanded configuration. The membrane may form a central lumen configuredto allow blood or other body fluids to pass therethrough. The treatmentsite may have a shape, and the lumen may have a shape that substantiallymatches the shape of the treatment site. Thus, the lumen may notsubstantially alter blood flow across the treatment site. In someembodiments, the lumen may have a substantially cylindrical shape. Thecylindrically shaped lumen may be formed from an invaginted portion ofthe personalized prosthesis. The membrane may comprise a resilientpolymer, and the polymer may be impermeable to blood. The membrane mayalso comprise an elongated neck portion, and invagiation of theelongated neck into the personalized prosthesis forms the central lumen.The prosthesis may also comprise one or more radiopaque markers coupledto the membrane or the self-expanding mesh for facilitating implantationof the prosthesis at the treatment site. The prosthesis may alsocomprise one or more apertures extending through a sidewall of theprosthesis. The one or more apertures may be fluidly coupled with thecentral lumen to allow blood flow or other fluids to flow between thecentral lumen and the one or more apertures. The one or more aperturesmay be configured to accommodate side branch vessels or other bodypassages such that the prosthesis does not obstruct blood flow or fluidflow therethrough. The prosthesis may also include a plurality of barbscoupled to either the mesh or the membrane, and the barbs may be adaptedto anchor the personalized prosthesis to the treatment site. Theprosthesis may have an end that is flared radially outward to engagetissue and help anchoring.

In yet another aspect of the present invention, a personalizedprosthesis for implantation at a treatment site in a patient maycomprise a self expanding membrane having a collapsed configuration andan expanded configuration. The collapsed configuration is adapted to bedelivered to the treatment site, and the expanded configuration isadapted to expand the personalized prosthesis into engagement with thetreatment site. In the expanded configuration the membrane ispersonalized to match the treatment site and has an outer surface thatsubstantially matches the treatment site shape and size. The membraneforms a central lumen configured to allow blood or other body fluids topass therethrough.

In another aspect of the present invention, a method for treatingdamaged or diseased tissue at a treatment site comprises providing animplantable prosthesis having a central lumen, an expanded configurationand a collapsed configuration. The implantable prosthesis is biased toexpand into the expanded configuration, and the implantable prosthesisis personalized to match shape of the treatment site. The central lumenis configured to allow blood flow or other body fluids to passtherethrough. The method also comprises advancing the implantableprosthesis in the collapsed configuration to the treatment site, andself-expanding the implantable prosthesis into the expandedconfiguration. In the expanded configuration the implantable prosthesishas a shape that substantially matches the shape of the treatment sitesuch that the implantable prosthesis expands substantially intoengagement with tissue at the treatment site. The prosthesis thenreinforces the tissue.

The implantable prosthesis may comprise a resilient polymer or aself-expanding wire mesh, and the mesh may be surrounded by a polymercover. The treatment site has a shape, and the lumen created by theprosthesis may have a shape that substantially matches the shape of thetreatment site. The lumen may also be cylindrically shaped, and thelumen may be disposed inside the implantable prosthesis. The lumen maynot substantially alter blood flow path across the treatment site.Advancing the implantable prosthesis may comprise advancing theimplantable prosthesis through a blood vessel. Radially expanding theimplantable prosthesis may comprise retracting a sheath away from theimplantable prosthesis, thereby allowing the implantable prosthesis toself-expand into the expanded configuration.

Reinforcing the tissue may comprise anchoring the implantable prosthesisto the tissue. The treatment site may comprise an aneurysm, andreinforcing the tissue may comprise preventing the aneurysm fromenlarging. The aneurysm may also be excluded by the prosthesis, and theprosthesis may be anchored with the tissue. Anchoring the prosthesis maycomprise engaging barbs on the implantable prosthesis with the tissue.Reinforcing the tissue may comprise constraining the tissue from movingradially outward or radially inward.

The method may optionally include aligning one or more radiopaquemarkers on a delivery device or on the prosthesis with one or moreanatomical features at the treatment site. The implantable prosthesismay comprise one or more apertures in a sidewall of the prosthesis, andthe method may comprise aligning the one or more apertures with one ormore corresponding side branch vessels or body passages at the treatmentsite. This prevents obstruction of the one or more side branch vesselsor the body passages. The implantable prosthesis may be sealed againstthe tissue at the treatment site to prevent blood flow therepast.

These and other aspects and advantages of the invention are evident inthe description which follows and in the accompanying drawings.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1A illustrates a normal abdominal aorta.

FIGS. 1B-1D illustrate various abdominal aortic aneurysms.

FIG. 1E illustrates a saccular aneurysm.

FIG. 2 illustrates a flow chart of an exemplary method of fabricating apersonalized prosthesis.

FIGS. 3A-3H illustrate exemplary methods of fabricating a personalprosthesis for treatment of an aneurysm.

FIG. 3I illustrates the prosthesis fabricated in FIGS. 3A-3H deployed inan aneurysm.

FIGS. 4A-4F illustrate an exemplary method of delivering a personalprosthesis to a treatment site.

FIGS. 5A-5C illustrate another exemplary embodiment of a personalizedprosthesis.

FIGS. 6A-6B illustrate an exemplary use of multiple prostheses.

FIG. 7 illustrates a juxtarenal aneurysm.

FIG. 8 illustrates a personalized prosthesis that accommodates sidebranch vessels.

FIG. 9 illustrates implantation of the prosthesis in FIG. 7 in ajuxtarenal aneurysm.

FIGS. 10A-10B illustrate an exemplary embodiment of a prosthesisaccommodating side branches.

FIG. 11 illustrates an exemplary mesh.

FIGS. 12A-12F illustrates exemplary mesh patterns.

FIG. 13 illustrates an exemplary embodiment of an end of a prosthesis.

FIG. 14 illustrates an exemplary mesh.

FIG. 15 illustrates another exemplary embodiment of a mesh pattern.

FIG. 16 illustrates yet another exemplary embodiment of a mesh.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be described in relation to an abdominalaortic aneurysm. However, one of skill in the art will appreciate thatthis is not intended to be limiting, and the devices and methodsdisclosed herein may be used in aneurysms in other parts of the bodysuch as in the brain, as well as used to treat other hollow anatomicalstructures including ducts, vessels, organs, or any other part of thebody where there is a need to reinforce a lumen, channel or other bodyspace. For example, a personalized prosthesis may be fabricated usingthe techniques described herein for implantation in or around thebladder in order to treat incontinence, or the prosthesis may bepersonalized to treat a diseased or damaged pyloric valve in thestomach, or other body passages such as a biliary duct.

FIG. 1A illustrates typical anatomy in a normal section of the abdominalaorta A where blood flows downstream as indicated by the arrow from theheart toward the legs. The aorta is typically a gradually taperingcylinder. A pair of renal arteries R branch off laterally from the aortaA and provide blood to the kidneys (not shown). The aorta bifurcatesinto two common iliac arteries I which then further bifurcate into theexternal iliac artery EI and the internal iliac artery II. After theexternal iliac arteries EI pass the inguinal ligament (not shown) theyare then generally referred to as the femoral arteries F. Thus, theaorta provides for smooth blood flow from the heart to the lowerextremities of the body.

However, in some cases, the tissue in the aorta may become weakened dueto disease or damage thereby resulting in a bulged region known as ananeurysm. The aneurysm may be at any point along the abdominal aorta.For example, FIG. 1B illustrates a suprarenal aortic aneurysm where theaneurysm AA is superior to (or upstream or above) the renal arteries R.FIG. 1C illustrates an infrarenal aneurysm AA which is inferior to (ordownstream or just below) the renal arteries and this type of aneurysmrepresents the majority of abdominal aortic aneurysms. FIG. 1C alsoillustrates that the aneurysm does not always remain strictly in theaorta, and that the aneurysm may extend into the iliac arteries andfemoral arteries. FIG. 1D illustrates a juxtarenal aortic aneurysm AAwhere the aneurysm extends over the portion of the aorta from which therenal arteries branch off. Each of the aneurysms illustrated in FIGS.1B-1D are referred to as fusiform aneurysms in which the weakened aortaand resulting bulge extend essentially all the way around the vessel.However, aneurysms may also be saccular in which only a portion of thevessel wall bulges outward, such as in FIG. 1E.

As discussed above, standard surgical procedures for aneurysm repair usea natural graft or an artificial graft typically made of Dacron™polyester or expanded polytetrafluorinated ethylene (ePTFE) to replacethe damaged or diseased section of the vessel. This procedure is highlyinvasive, can result in a number of post-operative complications, andrequires a lengthy recovery period. More recently, minimally invasiveendovascular repair techniques have been developed in which astent-graft is delivered to the treatment site. The stent-graft is thenradially expanded into the aneurysm thereby forming a new lumen forblood flow that excludes the aneurysm. While stent-grafts are promising,the implanted device may obstruct blood flow to side branch vessels, orthe implant may be pushed downstream away from the treatment site due tothe force of the blood and its pulsating nature. This is sometimesreferred to as “windsocking.”

Additionally, stent-grafts do not always seal perfectly against thevessel wall, thereby allowing blood to continue to pressurize theaneurysm sac. Endoleaks are a major cause of failure in the treatment ofaneurysms with stent-grafts. Endoleaks have been classified into severalcategories including Type I endoleaks where blood flows into theaneurysm sac due to incomplete sealing at the proximal end of thestent-graft. The proximal end as used herein with respect to theprosthesis, is the end closest to the heart, and the distal end of theprosthesis is the downstream end. When referring to a delivery systemused to deliver a prosthesis, the proximal end of the delivery system isthe end that is furthest away from the heart and usually closest to theoperator, and the distal end is the closest to the heart and typicallyfurthest away from the operator. Type II endoleaks result when bloodflows into the aneurysm sac from collateral vessels. Type III endoleaksresult in blood flow into the aneurysm sac due to poor sealing betweenstent-graft joints or rupture of the stent-graft. Type IV endoleaksresult in blood flow into the aneurysm sac due to excessive or unwantedporosity in the stent-graft that permits blood to flow through thestent-graft into the aneurysm. Endoleaks may result from improperfitting or matching of the stent-graft to the patient's anatomy.

Thus it is clear that there is a need for a prosthesis that can be usedto treat aneurysms that has better anchoring to prevent windsocking andthat fits the aneurysm anatomy more accurately in order to minimize thepossibility of endoleaks and that maintains blood flow to side branchvessels. A personalized prosthesis will address at least some of theseissues. Current imaging systems can be linked with computer aided design(CAD) and computer aided manufacturing (CAM) systems to allow aprosthesis to be fabricated that matches the patient's anatomy.

FIG. 2 is a flow chart which illustrates an exemplary method offabricating a personalized prosthesis that can be used to treataneurysms or any other treatment region. The method includes obtainingone or more images 202 of the treatment region which in this case is ananeurysm. These images may be obtained using computerized tomography(CT), x-ray, angiography, magnetic resonance imaging (MRI), ultrasound,or other imaging techniques known to those of skill in the art. Theimages may be stored on any storage media such as a CD-rom, flash memorystick, etc., or the images may be stored in the cloud, on a remoteserver, or any other convenient and secure location. The images may betransferred to any of these locations using the Internet. Once theimages are stored, the images or the digital data representing theimages may be input 204 into a computer aided design/computer aidedmanufacturing (CAD/CAM) system. The CAD/CAM system then converts theimages into a digital data set that can then be translated intomachining instructions which are provided to a machining device such asa CNC lathe, mill, electrical discharge machine (EDM), etc. and themachining instructions are used by the machining device to machine 206or otherwise form a mandrel or a mold having a shape that substantiallymatches the shape and volume of the treatment region. Thus the contoursof the mandrel will match the contours of the treatment region, and themandrel will substantially fill the volume of the treatment region,typically a body cavity, lumen, or other passage. The CAD/CAM system maybe programmed to compensate for the thickness of materials that areapplied to the mandrel later on, thus the mandrel may be slightlysmaller than the actual size of the treatment region. In otherembodiments, the mandrel shape will match the contours of the treatmentregion without compensating for material thickness. In both cases, theresulting mandrel shape substantially matches the treatment region shapeand size, and the mandrel will substantially fill the volume of thetreatment region. For example, in the case of an abdominal aorticaneurysm, the mandrel will substantially fill the volume of theaneurismal sac as well as a portion of the aneurysm neck and legs.

Once the mandrel is formed, it can be used as a master mold from which apersonal prosthesis is fabricated. The personal prosthesis will thenhave a size and shape that substantially matches the treatment regionwhich allows the personal prosthesis to anchor itself at the treatmentregion and prevent endoleaks and windsocking. A wire mesh is eitherpre-made 208 or otherwise provided. The mesh is preferably tubular andcylindrically shaped with both ends open so that the mesh may beslidably disposed over the mandrel like a sock, or in other embodimentsthe wire mesh may be wound 210 on the mandrel. The mesh and mandrel arethen placed in a furnace, oven, salt bath, etc. to an elevatedtemperature for a desired time. The mesh and mandrel are then removedand cooled using a prescribed cooling procedure such as air cooling,quenching in oil or water, etc. This heat treats 212 the wire mesh andthe wire mesh takes a set to the shape of the mandrel. Heat treating ofmetals, in particular self-expanding metals is known in the art. Theformed mesh is then removed from the mandrel. In this embodiment, or anyof the embodiments disclosed herein the wire mesh is preferablyself-expanding, and may be made from metals such as superelasticnitinol, and thus the mesh will have an expanded configuration whichmatches the mandrel and hence also substantially matches the shape ofthe treatment region. When tension is applied to the ends of the mesh,the mesh will collapse into a collapsed configuration which has a lowerprofile and is suitable for loading onto a delivery catheter forendovascular delivery to the treatment region. The wire mesh in this orany of the embodiments described herein may also be a shape memory alloysuch as nitinol such that placement of the mesh in a patient's bodyheats the mesh above a transition temperature and causes the mesh toradially expand outward. In still other embodiments, the mesh may beballoon expandable, so it may be delivered over an expandable membersuch as a balloon. When the balloon is expanded, the mesh similarlyexpands with the balloon.

Once the wire mesh has been heat treated, a fabric or polymer coatingmay be applied 214 to the wire mesh. The coating may be Dacron®polyester, expanded polytetrafluorinated ethylene (ePTFE), silicone,polyurethane, or other materials known in the art. The coating may be asheet or tube of the material coupled to the mesh with adhesives,sutures, encapsulation, etc., or the mesh may be dip coated in order toapply the polymer to the mesh. The coating is preferably biocompatibleand impermeable to blood or other body fluids. It may also bebiodegradable and be made of materials such as polylactic acid (PLA) orpolyglycolic acid (PGA). The resulting wire mesh with polymer coatingforms a personalized implantable prosthesis having a shape that matchesthe treatment region and substantially fills the volume of the treatmentregion, in this case, the aneurismal sac. In other embodiments, the wiremesh remains uncoated and uncovered and forms the personalizedprosthesis. The personalized implantable prosthesis is then coupled to adelivery system 215 such as a delivery catheter, and the system is thencleaned, packaged, and terminally sterilized 216 using manufacturingprocesses known to those of skill in the art. For example, packaging maycomprise placing the prosthesis in a procedure tray and sealing the traywith a Tyvek® lid, and terminally sterilizing the prosthesis maycomprise gassing the prosthesis with ethylene oxide, autoclaving it withsteam, or irradiating it with gamma or electron beam irradiation. Inalternative embodiments, the coating may be applied directly to themandrel without the mesh, thereby forming the prosthesis.

In some embodiments, the physician optionally may then confirm 218 thatthe resulting personal prosthesis is indeed the correct one for aparticular patient prior to shipping the prosthesis from the factory.The verification may be conducted visually over the Internet byverifying size, shape, or dimensions of the prosthesis. Once theverification is complete, the personal prosthesis may be shipped 219from the manufacturing facility to the doctor at a hospital,surgicenter, clinic or other place of business. Once received, thedoctor may then optionally re-verify 220 that the prosthesis is thecorrect size and shape for the patient prior to opening up the sterilepackage. If the prosthesis is incorrect, it may be returned to themanufacturing facility. Verification may be accomplished by scanning abar code and/or using the Internet. Once verification is complete, thepersonal prosthesis may be implanted 222 in the appropriate patient. Oneof skill in the art will also appreciate that appropriate patientprivacy must be maintained during the entire personalized manufacturingprocess as required by the Health Insurance Portability andAccountability Act (HIPAA). In an alternative embodiment, the mesh alonemay be formed over the mandrel and then delivered as described herein totreat the diseased or damaged tissue. Similarly, in another alternativeembodiment, a resilient polymer may be formed directly over thepersonalized mandrel without the mesh. This may then be used to treatthe diseased or damaged tissue as described herein.

FIGS. 3A-3I illustrate exemplary methods of fabricating a personalprosthesis for treatment of an aneurysm. FIG. 3A illustrates aninfrarenal aneurysm AA similar to that illustrated in FIG. 1C above.Using the fabrication technique described above, images of the aneurysmmay be obtained using CT scans, or any of the other techniques describedherein or known in the art. The image is then used to create a mandrel302 having a surface 304 which substantially matches the contours of theinner wall of the aneurysm as shown in FIG. 3B. As described above, themandrel may be made slightly undersized in order to accommodate formaterial thicknesses that are disposed on top of the mandrel. In somesituations, the mandrel may be made oversized if needed. The mandrel maybe made from stainless steel, aluminum, or any other material thatresists the heat experienced during heat treatment. Once the mandrel ismade, a wire mesh 306 may be disposed over the mandrel such that themesh takes the shape of the mandrel and hence the mesh then also has ashape which substantially matches the shape of the aneurysm. The wiremesh 306 may be pre-fabricated into a tubular sock-like shape that canbe easily placed over the mandrel as seen in FIG. 3C, or in otherembodiments, the wire mesh may be wound and formed over the mandrel. Instill other embodiments, such as seen in FIGS. 3D-3F, a flat preformedmesh 306 a (best seen in FIG. 3D) may be wrapped around the mandrel 302as seen in FIG. 3E. Once wrapped, the ends of the flat mesh may beaffixed to one another using methods known in the art such as welding,suturing, tying, bonding, soldering, etc. The mesh is thencircumferentially disposed around the mandrel as seen in FIG. 3F. Aribbon, wire, or other filament may be wrapped over the mesh to ensurethat it contacts the mandrel. FIG. 3G illustrates the wire mesh disposedover the mandrel. The mandrel and mesh are then heat treated asdescribed previously so that the wire mesh takes a set to the shape ofthe mandrel. The mesh is preferably nitinol and is self expanding, thusthe mesh may be collapsed into a collapsed configuration for delivery,and the wire mesh may self-expand into an expanded shape which matchesthe mandrel and the aneurysm shape. After heat treatment is completed,the mesh and mandrel may be dip coated with a polymer, or the polymer orfabric cover 310 may be applied to the mesh using methods describedabove or known to those of skill in the art. The polymer or fabric cover310 is preferably impermeable to blood to prevent blood from flowingacross the wall of the prosthesis. Radiopaque markers 308 or otherindicator markers are optionally attached to the polymer or fabric coverand/or to the wire mesh. The personal prosthesis is now complete andwill substantially match the anatomy of the aneurysm. This allows theprosthesis to seat itself in the aneurysm thereby anchoring theprosthesis in position, and further excludes the aneurysm from bloodflow, thereby preventing endoleaks. FIG. 3H illustrates the personalprosthesis with markers 308 once the mandrel has been removed. Thedevice can then be loaded onto a delivery catheter or other deliverydevice and implanted at the site of the infrarenal aneurysm as seen inFIG. 3G. Additional details about prosthesis delivery and implantationare described below.

FIGS. 4A-4F illustrate an exemplary method of delivering a personalizedprosthesis that is fabricated to match the patient's anatomy at thetreatment site. The personalized prosthesis is preferably fabricatedusing the methods described herein. This exemplary method is directed attreatment of an aortic aneurysm, but could also be used to treataneurysms in other parts of the body such as a cerebral aneurysm, orother body cavities such as a stomach, bladder, etc.

FIG. 4A illustrates an infrarenal aortic aneurysm AA in a portion of theaorta inferior to the renal arteries R. In this embodiment, the aneurysmdoes not extend into the iliac arteries I, external iliac arteries EI,internal iliac arteries II, or femoral arteries F. Thus, in this casethe repair of the prosthesis does not need to extend past the aorticbifurcation into the iliac arteries I. However, in the situation wherethe diseased or damaged tissue extends past the aortic bifurcation, asimilarly personalized prosthesis may be fabricated using similarmethods described above. The prosthesis may be a single piece or it maybe modular and assembled in situ. In FIG. 4B a standard guidewire GW isinserted by surgical cutdown or percutaneously (e.g. using the Seldingertechnique) into a femoral artery and then advanced so that the distaltip of the guidewire is positioned beyond the location of the aneurysm.

A delivery device such as a catheter 402 carrying the prosthesis canthen be advanced over the guidewire GW so that the distal portion 404 ofthe delivery catheter 402 is positioned beyond the location of theaneurysm and preferably is upstream or superior to the proximal end(closest to the heart) of the aneurysm, as illustrated in FIG. 4C. Nowreferring to FIG. 4D, the delivery device may include an inner shaft 409which carries the prosthesis 406, and an outer sheath 403 whichconstrains the prosthesis from expansion during delivery. The deliverydevice may have radiopaque markers (not shown) or other indicators tofacilitate visualization, alignment, and delivery, or optionalradiopaque markers or other indicators on the prosthesis itself may beused to help position the device. Once the delivery catheter isappropriately positioned relative to the aneurysm, the outer sheath 403may be retracted proximally (toward the physician operator) to exposethe personalized prosthesis 406 having a mesh 408 and polymer cover 410.When referring to the catheter, the term proximally refers to a positionclosest to the physician operating the catheter, and distal refers to aposition furthest away from the physician operating the catheter. Whenreferring to the aneurysm or the prosthesis, a proximal portion of theaneurysm or prosthesis is the portion closest to the heart (alsoreferred to as upstream), and the distal portion of the aneurysm orprosthesis is furthest away from the heart (also referred to asdownstream). The prosthesis 406 is a personalized prosthesis that hasbeen manufactured to match the anatomy of the treatment site using themethods described herein. The prosthesis 406 may be any of theembodiments of prostheses described herein. Retraction of the outersheath 403 as indicated by the arrows in FIG. 4D removes the constraintfrom the prosthesis 406 thereby allowing the prosthesis to self-expandinto engagement with the walls of the aorta upstream of the aneurysm.Thus, an upstream portion 412 of the prosthesis 406 radially expandsoutward into engagement with the aneurysm. The outer sheath 403 isfurther retracted until as indicated by the arrows in FIG. 4E until theentire prosthesis 406 is free of a constraint, and thus the prosthesis406 radially expands into engagement with the walls of the aneurysm andpreferably above and below the aneurismal sac as well. Once theprosthesis has been delivered, the delivery catheter and guidewire maybe removed from the patient leaving only the prosthesis 406 behind, asseen in FIG. 4F. Because the prosthesis 406 has been personalized tomatch the contours of the aneurysm, the prosthesis will expand tosubstantially fill the entire aneurismal sac and the prosthesis willengage the walls of the aneurysm over the entire treatment region.

Filling the entire sac and having engagement of the prosthesis with thewalls of substantially all of the aneurysm securely anchors theprosthesis in position thereby preventing migration, and also ensuresgood sealing between the prosthesis and the vessel. This preventsendoleaks and thus excludes the aneurysm from blood flow, therebyalleviating pressure on the weakened walls of the aneurysm whichprevents further dilation. Thus the personalized prosthesis reinforcesthe aneurysm. Additionally, in some aneurysms there may be muralthrombus on the walls of the aneurysm. Implanting a personalizedprosthesis that matches the contours of the aneurysm helps to trap anymural thrombus between the prosthesis and the aneurismal wall, therebypreventing the mural thrombus from embolizing. Additionally, endothelialcells will cover the prosthesis and further facilitate anchoring of thedevice in position. Endothelialization begins about two weeks afterimplantation, and is substantially complete after approximately twomonths. The prosthesis in FIGS. 4A-4F reinforce the walls of theaneurysm and alleviates the pressure from blood flow through theaneurysm, thereby preventing the aneurysm from further dilation. No newlumen is created in this embodiment, the blood flows through a path thatis substantially similar to its original path and that no longercontacts the wall of the aneurysm due to the walls of the personalizedprosthesis. However, in some circumstances, it may be beneficial tocreate a new lumen for blood flow. The new lumen may further preventexertion of blood pressure against the walls of the aneurysm, or mayrestore natural blood flow or hemodynamics back to, or close topre-aneurismal conditions.

FIGS. 5A-5C illustrate an exemplary embodiment of a personalizedprosthesis that forms a new lumen for blood flow. The aneurysm is imagedas described previously, and the corresponding mandrel is alsomanufactured to match the aneurysm similarly as described above. Oncethe mandrel is fabricated, the mesh and/or polymer may also be appliedto the mandrel as discussed above. In this embodiment, the resultingprosthesis 502 includes a main body section 504 that matches the sizeand shape of the aneurysm, and also includes an elongated neck portion506. In FIG. 5B, the elongated neck 506 may be invaginated as indicatedby the arrows such that the elongated neck portion 506 becomes disposedinside the main body portion 504. The space 510, the neck portion 506,and the inside wall of the prosthesis 502 may be left as is, or it maybe filled with a fluid, solid, or other material. The elongated neckportion 506 which preferably is a cylindrically shaped tube can now actas a lumen for blood flow therethrough. The free end 508 of theelongated neck 506 may be left as is, or it may be anchored to preventflapping. Anchoring may be accomplished with a stent, sutures, staples,or it may be sized such that the blood pressure opens the free end upfully and lodges it against a downstream and inner portion of theprosthesis. The free end 508 may also be sealed with the prosthesis incase the space 510 is filled with a material. FIG. 5C illustrates thepersonalized prosthesis of FIG. 5B once it has been delivered into aninfrarenal aortic aneurysm AA. This embodiment allows creation of alumen which more accurately matches the natural blood flow path beforethe aneurysm enlarged the blood flow path. Delivery of the personalizedprosthesis may be by any of the methods described herein.

In the embodiment of FIGS. 4A-4F a single prosthesis is delivered to theaneurysm. However, in other embodiments, more than one prosthesis may bedelivered. Using multiple prostheses facilitates delivery of theprosthesis since a single, low profile device may be delivered. Multipleprostheses are then delivered on top of one another, or axially spacedapart from one another in order to provide the desired coverage andsupport. For example, FIGS. 6A-6B illustrate the use of two prostheses.

The prostheses in FIGS. 6A-6B may be delivered in substantially the samemanner as previously described above, one after the other. A firstpersonalized prosthesis 1504 is delivered to the aneurysm AA and allowedto expand into engagement with the wall 1502. A second personalizedprosthesis 1506 is then serially delivered afterward so that it sitsinside the first prosthesis 1504. FIG. 6B illustrates a cross-sectiontaken along the line B-B in FIG. 6A and shows the two prosthesesadjacent one another in the aneurysm. This provides greater support tothe aneurysm and allows two lower profile prostheses to be deliveredinstead of a single higher profile device. Endothelialization of theprostheses will help anchor them into position. Endothelializationbegins about two weeks after implantation and is generally completeafter about two months. Multiple prostheses may be stacked inside oneanother, and/or they be placed end to end to cover a longer treatmentregion.

Other aneurysms may involve side branch vessels. A personalized meshprosthesis with a polymer or fabric coating may be used, but theprosthesis will obstruct blood flow into the side branch vessels. A meshonly personalized prosthesis may be used to solve this challenge,because a wire in the mesh may be disposed over the ostium of the sidebranch without substantially blocking blood flow to the side branch.Thus implanting a standard prosthesis to exclude the aneurysm couldobstruct the side branch vessels preventing proper blood flow. Forexample, a juxtarenal aneurysm AA is seen in FIG. 7 and extends acrosspart of the aorta A, and involves the renal arteries R. In thisexemplary aneurysm, the iliac arteries I, external iliacs EI, internaliliacs II, and femoral arteries F remain unaffected by the aneurysm.Implanting a prosthesis and excluding the aneurysm would obstruct bloodfrom flowing into the renal arteries resulting in damage to the kidneys.Thus, an improved and personalized prosthesis not only has a size andshape to match the anatomy of the treatment site, but also canaccommodate for side branch vessels, or other side branch lumens andpassageways.

FIG. 8 illustrates an exemplary embodiment of a personalized prosthesisthat can accommodate side branches such as the renal arteries. Thepersonalized prosthesis 702 includes a wire mesh 704 and an optionalpolymer or fabric cover 706 similar to previous embodiments describedherein. The prosthesis 702 may also optionally include radiopaquemarkers 708 to facilitate visualization and placement. The personalizedprosthesis may be fabricated in a similar manner as described above, andalso includes apertures 710 in a sidewall of the prosthesis that are influid communication with the central channel 712 of the prosthesis. Theside apertures are positioned along the prosthesis so that they matchthe location of the side branch vessels or body passages. The locationof the apertures is accurately determined based on the image obtained,such as a CT scan and the like. During manufacturing of the prosthesis,additional mandrels that extend laterally away from the main formingmandrel may be coupled with the main forming mandrel. This maintains theapertures in the wire mesh, and also maintains the apertures once themesh and mandrel are dip coated into a polymer, or when a polymer orfabric cover are otherwise applied to the mesh. The prosthesis 702 canthen be loaded into a delivery catheter as previously described. Theprosthesis is then deployed using the radiopaque markers so that theside apertures 710 align with the ostia of the side branch vessels. FIG.9 shows the prosthesis 702 deployed in the juxtarenal aneurysm of FIG.7, with the apertures 710 aligned with the ostia of the renal arteriesR. Thus blood flow is not only maintained through the prosthesis acrossthe aneurysm, but also to the renal arteries. The filaments in theprosthesis do not obstruct blood flow to the side branches. While thefilaments may partially cover the ostia, this is not significant enoughto affect blood flow.

FIGS. 10A-10B illustrate another embodiment of a personalized prosthesisthat accommodates for the renal arteries as well as other side branchvessels. In FIG. 10A the aneurysm AA is disposed in the aorta A andextends across the renal arteries R and also across other side branchvessels 1402 and 1403 that are between the iliac arteries I and therenal arteries R. The aneurysm is imaged as described before, and acentral mandrel matching the aneurysm is then fabricated. Additionalmandrels are laterally positioned where the renal arteries and the sidebranches are located. The mesh is then woven over the mandrel and aroundthe side branch mandrels so that an aperture is maintained at theirlocation. In alternative embodiments, the mesh is pre-woven and theloaded over the mandrel. The side branch mandrels are placed into themandrel to push the filaments of the mesh away thereby creating andpreserving openings for the renal or other side branches. After heattreating and other processing including putting an optional polymer orfabric coating over the mesh, a personalized prosthesis 1404 is producedas seen in FIG. 10B. Any of the mesh patterns disclosed herein may beused. The prosthesis then includes apertures 1406 that will match withthe ostia to the renal arteries, and also apertures 1408 and 1409 willmatch with the other two side branches. The apertures 1406, 1408 and1409 are in fluid communication with the central channel of theprosthesis so that blood flow will remain unobstructed to the renals orside branches. An optional radiopaque marker 1410 may also be includedon the prosthesis in order to help align the prosthesis with the renalarteries and side branches during delivery. The radiopaque marker mayinclude a long linear portion that indicates the longitudinal axis ofthe prosthesis. The radiopaque marker may be formed from a dense metalsuch as gold or platinum, or rhodium alloy that is coupled to the mesh.The renal arteries or other side branches themselves may be used duringalignment by injecting contrast media through the vessels whilevisualizing the prosthesis and surrounding vessels under fluoroscopy orusing other visualization techniques known in the art.

The personalized prostheses described above preferably include a wiremesh that self-expands to the personalized shape. Various wire patternsmay be used to create the mesh. For example, FIG. 11 illustrates a mesh902 having one or more filaments 904 which are spirally wound and anoptional polymer or fabric cover 906 is applied to the mesh. Thispattern of forming the mesh is advantageous because there is no overlapof the filaments, and the spiral pattern helps the mesh to be collapsedinto a low profile for delivery. FIGS. 12A-12F illustrate otherexemplary mesh patterns. FIG. 12A illustrates a mesh 1002 a having oneor more filaments 1004 a that interweave with one another similar totraditional fencing wire or chicken wire, to form a single overlappingor twisted region 1006 a. The overlap region is preferably in every rowand every column of the mesh where the filaments meet. The overlappingregion forms a protuberance which may be advantageous since theprotuberance may help embed the prosthesis into the tissue at thetreatment site thereby helping to anchor the prosthesis. Having a singleoverlap of the filaments helps the filaments move relative to oneanother thereby allowing the prosthesis to be easily collapsed which isdesirable during loading onto a delivery system and also helps to keepthe profile of the prosthesis minimal. This is also advantageous sinceit allows the prostheses to expand and collapse in concert with thepulsatile nature of the blood as it flows through the aorta or othervessel. However, in some circumstances, the single overlapping ortwisted region may not be secure enough to keep the mesh in its formedpattern or to provide adequate support to the aneurysm, especially whenthe prosthesis is under tension or compression because the wires in themesh may slip or slide relative to one another. The prosthesis undergoestension and compression during loading on a delivery system, duringdeployment, and after implantation due to the pulsatile nature of bloodflow.

FIG. 12B illustrates an alternative embodiment of a mesh pattern that ismore secure than the embodiment of FIG. 12A. Mesh 1002 b has one or morefilaments 1004 b that interweave with one another to form a doubleoverlapping or twisted region 1006 b. The overlap region is preferablyin every row and every column of the mesh where the filaments meet. Theoverlap region forms a protuberance similar to that in FIG. 12A and thusmay also be useful in anchoring the prosthesis. Having the doubleoverlapped or twisted region secures the filaments together more tightlyand thus helps prevents the filaments from slipping or sliding relativeto one another when the prosthesis is under tension or compression. Thusthe prosthesis retains its shape and provides more support than theembodiment in FIG. 12A. However, in some circumstances, the wires maystill slip or slide relative to one another, thus further securing ofthe filaments may be needed.

FIG. 12C illustrates still another embodiment of a mesh pattern whichhelps provide a stable mesh. The mesh 1002 c has one or more filaments1004 c that interweave with one another to form a triple overlapping ortwisted region 1006 c. The overlap region is preferably in every row andevery column of the mesh where the filaments meet. The overlap forms aprotuberance similar to those previously discussed and therefore may aidin anchoring of the prosthesis. Having the triple overlap or twistedregion secures the filaments together even more tightly than in theprevious embodiments and thus the filaments are further constrained fromslipping or sliding relative to one another when the prosthesis is undertension or compression. In some circumstances, having the triple overlapregion secures the filaments together tightly enough that they cannotmove at all relative to one another when the prosthesis is under tensionor compression. If the filaments cannot move at all relative to oneanother, this prevents the prosthesis from axially or radially expandingor contracting which interferes with its ability to be loaded in acollapsed configuration onto a delivery system, from expanding radiallyoutward upon deployment, or from expanding an contracting in concertwith the vessel wall due to pulsatile blood flow.

FIG. 12D illustrates a preferred embodiment of a hybrid mesh patternthat secures the filaments together securely so that the prosthesisholds its shape and provides good support during tension andcompression, and yet at the same time still allows some movement betweenthe filaments so that the prosthesis can expand and contract. Mesh 1002d has one or more filaments 1004 d that interweave with one another toform an alternating pattern of a triple overlap or twisted region 1006 dfollowed by three double overlapped or twisted regions 1008 d. Thepattern then repeats itself horizontally, and the next row shifts by onetwist to the right. Thus the triple twist in one row is offset from thetriple twist in the next row, followed by another double or twistedoverlap region 1008 d, and then the pattern repeats. The pattern repeatsso that everywhere the filaments overlap with one another, there iseither a double or triple overlap or twisted region. The overlap regionforms a similar protuberance as previously described which may be usefulfor anchoring the prosthesis. This hybrid weave has the advantages ofboth the double and triple overlap weaves previously described. Thus,the triple overlap regions secure the filaments together to minimizetheir movement relative to one another during compression or tension andthus the prosthesis holds its shape and provides good support, while atthe same time the double overlap regions allow some movement of thefilaments relative to one another thereby allowing the prosthesis toaxially and radially expand and contract during delivery, deployment,and after implantation. The weave preferably minimizes or substantiallyeliminates axial expansion and contraction while allowing radialexpansion and contraction.

FIGS. 12E-12F illustrates expansion and contraction of a personalizedprosthesis such as those described above using the weave of FIG. 12D.Without being bound by any particular theory, it is believed that thefilaments will remain tightly engaged with one another when theprosthesis 1002 d is under tension such as while the heart is in systoleas seen in FIG. 12E and represented by arrows 1018 d. Here, thefilaments 1004 d remain tightly wound together in both the doubleoverlap region 1008 d as well as the triple overlap region 1006 d. Thegap 1012 d between adjacent filaments wound together in a region 1008 dmay be represented by distance S1 and the pitch 1010 d or spacingbetween adjacent columns of wound filaments may be represented bydistance P1 during systole. When the prosthesis is compressed such aswhen the heart is in diastole, as indicated by arrows 1020 d in FIG.12F, the pitch or spacing 1014 d between adjacent columns of woundfilaments generally decreases relative to the expanded configuration.Moreover, the gap 1016 d between adjacent filaments wound together in adouble overlap region 1008 d increases relative to the when theprosthesis is in the expanded configuration thereby allowing thefilaments to slide relative to one another. The gap between adjacentfilaments wound together in a triple overlap region remain twistedtogether and there is substantially no relaxation. Thus, when viewingthe prosthesis laying on its side with its longitudinal axis horizontal,the triple-double-double-double horizontal weave pattern accommodatesthe motion of the aorta vessel wall caused by the pulsatile motion ofthe blood flowing through it. Of course, one of skill in the art willappreciate that this particular pattern is not intended to be limiting.Other patterns may be used including any combination or permutation ofthe single, double, triple, or more than three overlapping regions.

The filaments on the proximal and distal ends of the prosthesis may beterminated in any number of ways. FIG. 13 illustrates one exemplaryembodiment. The prosthesis 1602 has the triple-double-double-doubleweave pattern of FIGS. 12A-12F described above. The filaments mayterminate in an end region 1604 by twisting the filaments such that theyoverlap one another four times. One of skill in the art will appreciatethat this is not intended to be limiting and the number of overlappingregions may be one, two, three, four, five, six, or more. Additionally,the ends may remain extending axially outward to help anchor theprosthesis in tissue by partially piercing the tissue, or the ends maybe formed into curves, loops, or other shapes to prevent sharp ends fromprotruding and causing tissue trauma. This prevents the filaments frommoving relative to one another. Additionally, the end region 1604 maythen be bent slightly radially outward 1606 to form a skirt or flangedregion which flares outward and thus can embed into the vessel wall tohelp anchor the prosthesis.

In the embodiments of FIGS. 12A-12F, the weave pattern has beendescribed when the prosthesis is sitting on its side such that thelongitudinal axis of the prosthesis is generally horizontal. Thus, theweave pattern is generally parallel to the longitudinal axis, and thefilaments are weaved together in a horizontal pattern across theprosthesis and with a vertical orientation. In still other embodiments,the weave pattern of FIGS. 12A-12F may be rotated ninety degrees so thatthe filaments are weaved an orthogonal direction. FIG. 14 illustrates anexemplary embodiment of the weave pattern in FIG. 12A rotated ninetydegrees. The weave is illustrated with the prosthesis laying flat on itsside with its longitudinal axis generally horizontal. Thus, mesh 1202includes a plurality of filaments 1204 that are weaved together to forma single overlap or twisted region 1206. Other aspects of thisembodiment generally take the same form as in FIG. 12A. The otherembodiments described previously may also be weaved in a pattern thathas been rotated ninety degrees. Any of the mesh patterns describedherein may be formed into a round tubular member or the mesh may bewoven into a flat sheet and the ends may be joined together to form around tubular member. Additionally wires or filaments of differentdiameters may be combined with one other, or a single diameter may beused throughout a single mesh prosthesis in order to obtain desiredmechanical properties.

FIG. 15 illustrates still another pattern for the mesh 1102. Thispattern has one or more filaments 1104 woven into an undulating pattern.Adjacent rows of the undulating filaments are tied together with a wire,suture, or other tie 1106. Optionally, one or both ends of the tie 1106may be left uncut to form a barb 1108 that can also be used to helpanchor the prosthesis to tissue at the treatment site. Any of these wiremesh patterns with anchoring or without anchoring may be used in any ofthe embodiments described herein.

FIG. 16 illustrates yet another exemplary embodiment of a mesh. The mesh1302 includes one or more filaments 1304 which are formed into anundulating pattern having peaks and valleys. The peaks and valleys inone row of the mesh may overlap with the valleys and peaks of anadjacent row of the mesh. The overlapping portions may then be welded1306 together to keep the filaments coupled together. In alternativeembodiments, welds may be any combination of the previous meshembodiments.

In any of the embodiments described herein, the filament may be anycombination of wires having any cross-section such as round, square,rectangular, etc. and the size of the wire may be adjusted in order tovarious properties of the prosthesis such as its profile in thecollapsed configuration, its stiffness and strength, and otherproperties. In preferred embodiments, a round nitinol wire is usedhaving a diameter of 0.005 inches to 0.006 inches. Exemplary wirediameters of 0.005 inches, 0.0055 inches, and 0.006 inches may be used.

Additionally, any of the prostheses may carry a therapeutic agent suchas an antithrombotic agent, antibiotic, etc. for localized andcontrolled elution at the treatment site. One of skill in the art willalso appreciate that the prosthesis described herein preferably has amesh with a polymer or fabric cover disposed thereover, but theprosthesis could be a mesh only to support the damaged or diseasedtissue, or the prosthesis could be the polymer or fabric cover only.Thus, the fabrication methods and delivery methods described hereinapply to either embodiment of prosthesis.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

What is claimed is:
 1. A method for manufacturing a personalizedimplantable prosthesis in a manufacturing facility, said methodcomprising: providing one or more images of a treatment site in apatient; creating a digital data set characterizing shape and volume ofthe treatment site based on the one or more images; transforming thedigital data set into machining instructions; forming a mandrel usingthe machining instructions, wherein the mandrel has a shape thatsubstantially matches the treatment site shape; applying a mesh to themandrel; heat treating the mesh while the mesh is disposed over themandrel so that the mesh is biased to return to a shape matching theshape of the treatment site thereby forming the personalized implantableprosthesis, the personalized implantable prosthesis having a contractedconfiguration and an expanded configuration, wherein the personalizedimplantable prosthesis is adapted to be delivered to the treatment sitein the contracted configuration, and wherein the personalizedimplantable prosthesis is biased to return to the expandedconfiguration, the expanded configuration having a shape substantiallymatching the treatment site shape.
 2. The method of claim 1, whereinproviding the one or more images comprises providing one or morecomputerized tomography (CT) images, one or more magnetic resonanceimages (MRI), one or more x-ray images, one or more ultrasound images,or one or more an angiography images of the treatment site.
 3. Themethod of claim 1, wherein transforming the digital data set intomachining instructions comprises transferring the digital data set intoa CAD/CAM system.
 4. The method of claim 1, wherein forming the mandrelcomprises machining a piece of metal.
 5. The method of claim 1, whereinforming the mandrel comprises forming the mandrel so as to be undersizedrelative to the treatment site, the undersized mandrel accommodating forthickness of the mesh.
 6. The method of claim 1, wherein applying themesh to the mandrel comprises slidably disposing a mesh over themandrel.
 7. The method of claim 1, wherein applying the mesh to themandrel comprises wrapping a filament around the mandrel.
 8. The methodof claim 1, wherein applying the mesh to the mandrel comprises wrappinga preformed flat mesh therearound.
 9. The method of claim 1, whereinheat treating the mesh comprises heat treating a nitinol mesh.
 10. Themethod of claim 1, further comprising removing the mandrel from the meshand recovering the mesh.
 11. The method of claim 1, further comprisingforming at least one side aperture in the personalized implantableprosthesis, the at least one side aperture configured to be aligned witha side branch vessel in the treatment site.
 12. The method of claim 1,further comprising forming a membrane over the mesh thereby forming acover over the personalized implantable prosthesis.
 13. The method ofclaim 12, wherein forming the membrane comprises attaching a polymercover to the mesh.
 14. The method of claim 12, wherein forming themembrane comprises dip coating a polymer cover over the mesh.
 15. Themethod of claim 1, further comprising: mounting the implantableprosthesis on a delivery catheter; cleaning the prosthesis and deliverycatheter; packaging the implantable prosthesis; and terminallysterilizing the implantable prosthesis.
 16. The method of claim 1,further comprising requesting verification that the shape of thepersonalized implantable prosthesis is appropriate for implantation atthe treatment site before shipping the personalized implantableprosthesis from the manufacturing facility.
 17. The method of claim 16,wherein the verification is performed by a physician.
 18. The method ofclaim 16, wherein the verification is performed over the Internet. 19.The method of claim 1, further comprising shipping the personalizedimplantable prosthesis to a hospital.
 20. The method of claim 1, furthercomprising: mounting the personalized implantable prosthesis on adelivery catheter; placing the personalized implantable prosthesis andthe delivery catheter in packaging; sterilizing the personalizedimplantable prosthesis and the delivery catheter in the packaging; andrequesting verification that the personalized implantable prosthesis isappropriate for implantation at the treatment site before opening thesterile packaging.
 21. The method of claim 20, wherein the verificationis performed by a physician.
 22. The method of claim 20, wherein theverification is performed over the Internet.
 23. The method of claim 1,further comprising removing the implantable prosthesis from the mandrelso that a central lumen extends through the implantable prosthesis. 24.The method of claim 1, wherein the treatment site is an aneurysm.
 25. Apersonalized prosthesis for implantation at a treatment site, saidprosthesis comprising: a self-expanding mesh having a collapsedconfiguration and an expanded configuration, the collapsed configurationadapted to be delivered to the treatment site, and the expandedconfiguration adapted to expand the personalized prosthesis intoengagement with the treatment site, wherein the mesh in the expandedconfiguration is personalized to match the treatment site, wherein themesh has an outer surface that substantially matches the treatment siteshape and size in the expanded configuration, and wherein theself-expanding mesh forms a central lumen configured to allow blood orother body fluids to pass therethrough.
 26. The personalized prosthesisof claim 25, wherein the self-expanding mesh comprises a nitinol mesh.27. The personalized prosthesis of claim 25, wherein the self-expandingmesh comprises one or more filaments in a helical pattern.
 28. Thepersonalized prosthesis of claim 25, wherein the self-expanding meshcomprises one or more filaments woven together to form overlappingregions with the one or more filaments overlapping one another at leastonce.
 29. The personalized prosthesis of claim 25, wherein theself-expanding mesh comprises one or more filaments woven together toform a first overlapping region and a second overlapping region, whereinin the first overlapping region the filaments overlap with one another afirst number of times, and wherein in the second overlapping region thefilaments overlap with one another a second number of times differentthan the first number of times.
 30. The personalized prosthesis of claim25, wherein the self-expanding mesh comprises barbs or hooks adapted toengage tissue at the treatment site and anchor the personalizedprosthesis.
 31. The personalized prosthesis of claim 25, wherein theself-expanding mesh comprises a plurality of overlapping filamentsforming overlapping regions, and wherein the overlapping regions formraised surfaces adapted to engage tissue at the treatment site andanchor the prosthesis.
 32. The personalized prosthesis of claim 25,further comprising a membrane disposed over the mesh, wherein themembrane is elastic and conforms to the self-expanding mesh, and whereinthe membrane has an outer surface that substantially matches thetreatment site shape in the expanded configuration, and wherein themembrane forms the central lumen.
 33. The personalized prosthesis ofclaim 32, wherein the membrane comprises a resilient polymer.
 34. Thepersonalized prosthesis of claim 32, wherein the polymer is impermeableto blood.
 35. The personalized prosthesis of claim 32, wherein themembrane comprises an elongated neck portion, and wherein invaginationof the elongated neck into the personalized prosthesis forms the centrallumen.
 36. The personalized prosthesis of claim 25, further comprisingone or more radiopaque markers coupled to the membrane or theself-expanding mesh for facilitating implantation of the prosthesis atthe treatment site.
 37. The personalized prosthesis of claim 25, furthercomprising one or more apertures extending through a sidewall of theprosthesis, the one or more apertures fluidly coupled with the centrallumen to allow bloodflow or other fluids to flow between the centrallumen and the one or more apertures, the one or more aperturesconfigured to accommodate side branch vessels or other body passagessuch that the prosthesis does not obstruct blood flow or fluid flowtherethrough.
 38. The personalized prosthesis of claim 25, wherein thetreatment site has a shape, and wherein the lumen has a shapesubstantially matching the shape of the treatment site.
 39. Thepersonalized prosthesis of claim 25, wherein the lumen does notsubstantially alter blood flow path across the treatment site.
 40. Thepersonalized prosthesis of claim 25, wherein the lumen has a cylindricalshape.
 41. The personalized prosthesis of claim 40, wherein thecylindrically shaped lumen is formed from an invaginated portion of thepersonalized prosthesis.
 42. A personalized prosthesis for implantationat a treatment site of a patient, said prosthesis comprising: aself-expanding membrane having a collapsed configuration and an expandedconfiguration, the collapsed configuration adapted to be delivered tothe treatment site, and the expanded configuration adapted to expand thepersonalized prosthesis into engagement with the treatment site, whereinthe membrane in the expanded configuration is personalized to match thetreatment site, and wherein the membrane has an outer surface thatsubstantially matches the treatment site shape and size in the expandedconfiguration, and wherein the membrane forms a central lumen configuredto allow blood or other body fluids to pass therethrough.
 43. A methodfor treating damaged or diseased tissue at a treatment site, said methodcomprising: providing an implantable prosthesis having a central lumen,an expanded configuration and a collapsed configuration, and wherein theimplantable prosthesis is biased to expand into the expandedconfiguration, and wherein the implantable prosthesis is personalized tomatch shape of the treatment site, and wherein the central lumen isconfigured to allow blood flow or other body fluids to passtherethrough; advancing the implantable prosthesis in the collapsedconfiguration to the treatment site; self-expanding the implantableprosthesis into the expanded configuration, wherein in the expandedconfiguration the implantable prosthesis has a shape that substantiallymatches the shape of the treatment site such that the implantableprosthesis expands substantially into engagement with tissue at thetreatment site; and reinforcing the tissue with the implantableprosthesis.
 44. The method of claim 43, wherein the implantableprosthesis comprises a self-expanding wire mesh surrounded by a polymercover.
 45. The method of claim 43, wherein the implantable prosthesiscomprises a self-expanding wire mesh.
 46. The method of claim 43,wherein the implantable prosthesis comprises a resilient polymer. 47.The method of claim 43, wherein the treatment site has a shape, andwherein the lumen has a shape substantially matching the shape of thetreatment site.
 48. The method of claim 43, wherein the lumen has acylindrical shape.
 49. The method of claim 48, wherein the lumen isformed from an invaginated portion of the implantable prosthesis. 50.The method of claim 48, wherein the cylindrically shaped lumen isdisposed inside the implantable prosthesis.
 51. The method of claim 43,wherein the lumen does not substantially alter blood flow path acrossthe treatment site.
 52. The method of claim 43, wherein advancing theimplantable prosthesis comprises advancing the implantable prosthesisthrough a blood vessel.
 53. The method of claim 43 wherein radiallyexpanding the implantable prosthesis comprises retracting a sheath awayfrom the implantable prosthesis, thereby allowing the implantableprosthesis to self-expand into the expanded configuration.
 54. Themethod of claim 43, wherein reinforcing the tissue comprises anchoringthe implantable prosthesis to the tissue.
 55. The method of claim 43,wherein the treatment site comprises an aneurysm, and reinforcing thetissue comprises preventing the aneurysm from enlarging.
 56. The methodof claim 43, wherein the treatment site comprises an aneurysm andreinforcing the tissue comprises excluding the aneurysm.
 57. The methodof claim 43, wherein reinforcing the tissue comprises anchoring theimplantable prosthesis with the tissue.
 58. The method of claim 57,wherein anchoring the implantable prosthesis comprises engaging barbs onthe implantable prosthesis with the tissue.
 59. The method of claim 43,wherein reinforcing comprises constraining the tissue from movingradially outward or radially inward.
 60. The method of claim 43, whereinthe implantable prosthesis comprises one or more radiopaque markers, themethod further comprising aligning the one or more radiopaque markerswith one or more anatomical features at the treatment site.
 61. Themethod of claim 43, wherein the implantable prosthesis comprises one ormore apertures in a sidewall thereof, the method further comprisingaligning the one or more apertures with one or more ostia of sidebranchvessels or body passages at the treatment site, thereby preventingobstruction of the one or more sidebranch vessels or the body passages.62. The method of claim 43, further comprising sealing the implantableprosthesis against the tissue at the treatment site to prevent bloodflowtherepast.